SFRP4

secreted frizzled related protein 4, the group of Secreted frizzled-related proteins

Basic information

Region (hg38): 7:37905931-38025695

Links

ENSG00000106483 ∙ NCBI:6424 ∙ OMIM:606570 ∙ HGNC:10778 ∙ Uniprot:Q6FHJ7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Pyle disease (Supportive), mode of inheritance: AR
• Pyle disease (Moderate), mode of inheritance: AR
• Pyle disease (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyle disease	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	27355534

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SFRP4 gene.

• not provided (78 variants)
• Inborn genetic diseases (17 variants)
• Pyle metaphyseal dysplasia (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SFRP4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				20	6	26
missense		2	47	1	2	52
nonsense	2					2
start loss			1			1
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	1	1	5
non coding				5		5
Total	4	2	49	26	8

Highest pathogenic variant AF is 0.0000131

Variants in SFRP4

This is a list of pathogenic ClinVar variants found in the SFRP4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-37907482-C-G			Benign (Jan 15, 2024)
7-37907486-CTT-C			Uncertain significance (May 29, 2021)
7-37907496-T-A		Inborn genetic diseases	Uncertain significance (Jul 27, 2021)
7-37907501-C-T		Pyle metaphyseal dysplasia • SFRP4-related disorder	Benign (Jan 31, 2024)
7-37907519-G-A		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
7-37907562-G-T		Pyle metaphyseal dysplasia • SFRP4-related disorder	Benign (Jan 31, 2024)
7-37907573-G-T		Inborn genetic diseases	Uncertain significance (Aug 15, 2022)
7-37907582-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
7-37907591-C-T			Uncertain significance (May 12, 2022)
7-37907604-C-T		Inborn genetic diseases	Uncertain significance (Jun 17, 2022)
7-37907605-G-A		SFRP4-related disorder	Benign/Likely benign (May 09, 2023)
7-37907606-G-A			Uncertain significance (Aug 04, 2023)
7-37907609-G-C		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
7-37907636-C-T		Inborn genetic diseases	Likely benign (Sep 29, 2023)
7-37907653-C-T			Likely benign (Feb 25, 2023)
7-37909611-A-ACTTACTATGGATCTTTTACTAAGCTGATCTCTCCATTTTTCAAC			Uncertain significance (Sep 07, 2022)
7-37909618-A-G			Uncertain significance (Aug 06, 2022)
7-37909638-A-C			Uncertain significance (Apr 13, 2021)
7-37909673-G-A			Uncertain significance (Jul 19, 2022)
7-37909680-C-T			Uncertain significance (Sep 26, 2022)
7-37909681-C-T			Likely pathogenic (Jul 28, 2023)
7-37909683-GA-G			Benign (Apr 16, 2022)
7-37909692-T-A			Likely benign (Jan 15, 2024)
7-37909698-T-C			Likely benign (Oct 03, 2022)
7-37912111-G-A			Likely benign (May 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SFRP4	protein_coding	protein_coding	ENST00000436072	6	119755

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000926	0.942	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0459	210	212	0.991	0.0000114	2285
Missense in Polyphen		81	85.546	0.94686		965
Synonymous	0.188	75	77.1	0.973	0.00000418	646
Loss of Function	1.72	9	16.6	0.543	7.73e-7	180

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000739	0.000739
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927). {ECO:0000250|UniProtKB:Q9JLS4, ECO:0000250|UniProtKB:Q9Z1N6, ECO:0000269|PubMed:12952927}.
• Disease: DISEASE: Pyle disease (PYL) [MIM:265900]: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures. {ECO:0000269|PubMed:27355534}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Adipogenesis;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Wnt Signaling Pathway;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.254

Intolerance Scores

• loftool: 0.642
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.188
• hipred: Y
• hipred_score: 0.557
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.121

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sfrp4
• Phenotype: respiratory system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: positive regulation of receptor internalization;negative regulation of cell population proliferation;response to hormone;positive regulation of gene expression;cell differentiation;negative regulation of Wnt signaling pathway;regulation of BMP signaling pathway;non-canonical Wnt signaling pathway;positive regulation of apoptotic process;negative regulation of DNA-binding transcription factor activity;positive regulation of epidermal cell differentiation;phosphate ion homeostasis;canonical Wnt signaling pathway;bone morphogenesis;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of keratinocyte apoptotic process;negative regulation of non-canonical Wnt signaling pathway;negative regulation of sodium-dependent phosphate transport
• Cellular component: extracellular space;nucleus;cytoplasm;cell surface
• Molecular function: protein binding;Wnt-protein binding